A systematic review and integrated analysis of biologics that target Type 2 inflammation to treat COPD with increased peripheral blood eosinophils

BACKGROUND AND AIMS: Biologics that target Type 2 inflammation are effective in reducing exacerbations of severe asthma. We conducted a systematic review and integrated analysis of the efficacy and safety of these biologics in chronic obstructive pulmonary disease (COPD) patients with increased peripheral blood eosinophils. METHODS: Clinical trials of biologics that target Type 2 inflammation in COPD were found using PubMed, the Cochrane Library, and ClinicalTrials.gov. We analyzed the clinical efficacy of anti-IL-5-targeted therapy at approved (benralizumab 30 mg, mepolizumab 100 mg, for severe asthma) and high (benralizumab 100 mg, mepolizumab 300 mg) doses. RESULTS: Approved benralizumab and mepolizumab doses tended to reduce moderate-to-severe exacerbations by 9% [risk ratio (RR) 0.91, 95% confidence interval (CI) [0.83, 1.00], p = 0.05], but did not reduce exacerbations requiring emergency department visits or hospitalization. High-dose benralizumab and mepolizumab reduced moderate-to-severe exacerbations by 12% (RR = 0.88, 95% CI [0.80, 0.98], p = 0.02) and exacerbations requiring emergency department visits or hospitalization by 33% (RR = 0.67, 95% CI [0.53, 0.84], p = 0.0005). Neither dose improved St. George's Respiratory Questionnaire or COPD Assessment Test scores. The safety of benralizumab and mepolizumab was comparable to placebo. CONCLUSIONS: Benralizumab and mepolizumab have limited efficacy in reducing moderate-to-severe exacerbations in COPD patients with increased peripheral blood eosinophils and requires at least high doses.